Prognostic role of serum levels of hTERT, VEGF, and EGFR in metastatic colorectal cancer

Sirera, Rafael; Camps, Carme; Blasco, Ana; Cabrera, Alejandro; Safont, M.J.; Iranzo, Vega; Cayuela, D.; Caballero, Cristina; Gil, M. G.; Lorca, Javier Arellano

doi:10.1200/jco.2008.26.15_suppl.15075

Cited by 2 publications

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“…hTERT is only expressed in immortalized cells and most tumor cells but not in normal somatic cells (Liu et al, 2006). hTERT is expressed in many cancer types (including CRC) and plays a crucial role in oncogenesis by providing proliferation, survival and anti-apoptotic signals necessary for tumor progression (Sirera et al, 2008;Loyon et al, 2019). hTERT can regulate CRC via multiple pathways; for example, hTERT can be upregulated at the mRNA and protein level by KRT23 to promote CRC growth (Zhang N. et al, 2017), and CRC proliferation can be increased through the circFMN2/miR-1182/hTERT axis (Li et al, 1979).…”

Section: Introductionmentioning

confidence: 99%

hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression

Gong

Yang

Wang

et al. 2021

Front. Cell Dev. Biol.

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High human telomerase reverse transcriptase (hTERT) expression is related to severe Colorectal Cancer (CRC) progression and negatively related to CRC patient survival. Previous studies have revealed that hTERT can reduce cancer cellular reactive oxygen species (ROS) levels and accelerate cancer progression; however, the mechanism remains poorly understood. NFE2-related factor 2 (NRF2) is a molecule that plays a significant role in regulating cellular ROS homeostasis, but whether there is a correlation between hTERT and NRF2 remains unclear. Here, we showed that hTERT increases CRC proliferation and migration by inducing NRF2 upregulation. We further found that hTERT increases NRF2 expression at both the mRNA and protein levels. Our data also revealed that hTERT primarily upregulates NRF2 by increasing NRF2 promoter activity rather than by regulating NRF2 mRNA or protein stability. Using DNA pull-down/MS analysis, we found that hTERT can recruit YBX1 to upregulate NRF2 promoter activity. We also found that hTERT/YBX1 may localize to the P2 region of the NRF2 promoter. Taken together, our results demonstrate that hTERT facilitates CRC proliferation and migration by upregulating NRF2 expression through the recruitment of the transcription factor YBX1 to activate the NRF2 promoter. These results provide a new theoretical basis for CRC treatment.

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Section: Introductionmentioning

confidence: 99%

hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression

Gong

Yang

Wang

et al. 2021

Front. Cell Dev. Biol.

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show abstract

“…hTERT is only expressed in immortalized cells and most tumor cells but not in normal somatic cells [5]. hTERT is expressed in many cancer types (including CRC) and plays a crucial role in oncogenesis by providing proliferation, survival and anti-apoptotic signals necessary for tumor progression [6,7]. hTERT can regulate CRC via multiple pathways; for example, hTERT can be upregulated at the mRNA and protein level by KRT23 to promote CRC growth [8], and CRC proliferation can be increased through the circFMN2/miR-1182/hTERT axis [9].…”

Section: Introductionmentioning

confidence: 99%

hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression

Gong

Yang

Wang

et al. 2021

Preprint

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Background: High human telomerase reverse transcriptase (hTERT) expression is related to severe Colorectal Cancer (CRC) progression and negatively related to CRC patient survival. Previous studies have revealed that hTERT can reduce cancer cellular Reactive Oxygen Species (ROS) levels and accelerate cancer progression; however, the mechanism remains poorly understood. NFE2‑related factor 2 (NRF2) is a molecule that plays a significant role in regulating cellular ROS homeostasis, but whether there is a correlation between hTERT and NRF2 remains unclear. Herein, we sought to determine the relationship of hTERT and NRF2 in the progression of CRC and to elucidate the underlying molecular mechanisms.Methods: qPCR, Western blot, Immunohistochemistry, immunofluorescence assays were used to detect the mRNA and protein expression of hTERT, NRF2 and YBX1 in CRC cell lines and tissues.CCK8 and colony formation were used to detect the proliferation of CRC cells, transwell assay was used to detect the migration of CRC cells. Dual-luciferase reporter assays were used to detect the promoter activity of NRF2. DNA pull-down/MS analysis was used to identify NRF2 promoter binding proteins. ChIP-qPCR was used to detect the YBX1binding sequences of NRF2 promoter.Results: Both hTERT and NRF2 are highly expressed in CRC tissues and associated with poor diagnosis. hTERT increases NRF2 expression at both the mRNA and protein levels. hTERT increases CRC proliferation and migration by inducing NRF2 upregulation. Moreover, hTERT primarily upregulates NRF2 by increasing NRF2 promoter activity rather than by regulating NRF2 mRNA or protein stability, and hTERT recruits YBX1 to upregulate NRF2 promoter activity thus increases NRF2 expression and enhances CRC proliferation and migration.Conclusions: hTERT facilitates CRC proliferation and migration by upregulating NRF2 expression through the recruitment of the transcription factor YBX1 to activate the NRF2 promoter.

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Prognostic role of serum levels of hTERT, VEGF, and EGFR in metastatic colorectal cancer

Cited by 2 publications

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hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression

hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression

hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression

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